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The Antioxidant Activity of Thymus serpyllum Extract Protects against the Inflammatory State and Modulates Gut Dysbiosis in Diet-Induced Obesity in Mice.

ABSTRACT: Nowadays, there is an increasing interest in alternative therapies in the treatment of metabolic syndrome that combine efficacy and safety profiles. Therefore, this study aimed to evaluate the effect of an extract of Thymus serpyllum, containing rosmarinic acid, on high-fat diet (HFD)-induced obesity mice, highlighting the impact of its antioxidant activity on the inflammatory status and gut dysbiosis. The extract was administered daily (50, 100 and 150 mg/kg) in HFD-fed mice. The treatment reduced body weight gain, glucose and lipid metabolic profiles. Moreover, the extract ameliorated the inflammatory status, with the c-Jun N-terminal kinases (JUNK) pathway being involved, and showed a significant antioxidant effect by the reduction of radical scavenging activity and the mitigation of lipid peroxidation. Moreover, the extract was able to modulate the altered gut microbiota, restoring microbial richness and diversity, and augmenting the counts of short-chain fatty acid producing bacteria, which have been associated with the maintenance of gut permeability and weight regulation. In conclusion, the antioxidant activity of Thymus serpyllum extract displayed a positive impact on obesity and its metabolic alterations, also reducing systemic inflammation. These effects may be mediated by modulation of the gut microbiota.

SUBMITTER: Ruiz-Malagon AJ

PROVIDER: S-EPMC9219752 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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The Antioxidant Activity of <i>Thymus serpyllum</i> Extract Protects against the Inflammatory State and Modulates Gut Dysbiosis in Diet-Induced Obesity in Mice.

Ruiz-Malagón Antonio Jesús AJ Rodríguez-Sojo María Jesús MJ Hidalgo-García Laura L Molina-Tijeras José Alberto JA García Federico F Pischel Ivo I Romero Miguel M Duarte Juan J Diez-Echave Patricia P Rodríguez-Cabezas María Elena ME Rodríguez-Nogales Alba A Gálvez Julio J

Antioxidants (Basel, Switzerland) 20220528 6

Nowadays, there is an increasing interest in alternative therapies in the treatment of metabolic syndrome that combine efficacy and safety profiles. Therefore, this study aimed to evaluate the effect of an extract of <i>Thymus serpyllum</i>, containing rosmarinic acid, on high-fat diet (HFD)-induced obesity mice, highlighting the impact of its antioxidant activity on the inflammatory status and gut dysbiosis. The extract was administered daily (50, 100 and 150 mg/kg) in HFD-fed mice. The treatme ...[more]

PMID: 35739969

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Project description:ObjectiveObesity represents a growing health problem that is reaching pandemic dimensions and lacks effective cures, thus highlighting an urgent need for better mechanistic understanding and new therapeutic strategies. Unlike transcription, the function of translation in obesity has hardly been investigated. Here, we fill this knowledge gap by pinpointing a crucial function for gene regulation at the step of translation in diet-induced obesity.MethodsWe performed studies with human adipose tissue, high-fat-diet-induced obese mice and rats, CPEB4-knockout mice, and adipocyte lines. Cells were transfected with small-interfering RNAs that knockdown CPEB4. Transcriptome-wide identification and validation of CPEB4 targets in adipocytes were obtained by RNA-protein coimmunoprecipitation and high-throughput sequencing. The effect of CPEB4 depletion on high-fat-diet-induced dysbiosis was determined by 16S ribosomal-RNA gene sequencing and microbiome bioinformatics.ResultsWe show that cytoplasmic polyadenylation element-binding protein 4 (CPEB4), which controls the translation of specific mRNAs by modulating their poly(A) tails, is highly expressed in visceral fat of obese but not lean humans and rodents (mice and rats), where it orchestrates an essential post-transcriptional reprogramming for aggravation of high-fat-diet-induced obesity. Mechanistically, CPEB4 overexpression in obese adipocytes activates the translation of factors essential for adipose tissue expansion (Cebpb, Stat5a) and adipocyte-intrinsic immune-like potential (Ccl2, Tlr4), as demonstrated by RNA-immunoprecipitation and high-throughput sequencing and experimentally validated in vivo. Consistently blocking CPEB4 production in knockout mice protects against diet-induced body weight gain and reduces adipose tissue enlargement and inflammation. In addition, the depletion of CPEB4 specifically in obese adipocytes using short hairpin RNAs decreases cell differentiation, lipid accumulation, and the proinflammatory and migratory capacity of macrophages. The absence of CPEB4 also attenuates high-fat diet-induced dysbiosis, shaping the microbiome composition toward a more beneficial profile, as shown by microbiome bioinformatics analysis.ConclusionOur study identifies CPEB4 as a driver and therapeutic target to combat obesity.

Dataset Information

The Antioxidant Activity of Thymus serpyllum Extract Protects against the Inflammatory State and Modulates Gut Dysbiosis in Diet-Induced Obesity in Mice.

Publications

The Antioxidant Activity of <i>Thymus serpyllum</i> Extract Protects against the Inflammatory State and Modulates Gut Dysbiosis in Diet-Induced Obesity in Mice.

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